| Objective:This paper retrospectively analyzed the second-generation sequencing results and prognosis of patients with acute myeloid leukemia(AML)in newly treated adults,and explored the characteristics of gene mutations in adult AML patients and the relevant factors affecting prognosis.Method:Clinical data of newly diagnosed patients with acute myeloid leukemia(excluding acute promyelocytic leukemia,APL)who were treated at the Second Affiliated Hospital of Nanchang University from January 2019 to February 2023 were collected.Next-generation sequencing(NGS)was used for gene mutation spectrum detection,and the following analyses were performed:1)general clinical characteristics of AML patients with gene mutations;2)distribution and characteristics of gene mutations;3)relationship between different gene mutations and their distribution in different age groups;4)Relationship between gene mutations and karyotype in AML patients;5)impact of gene mutations on the induction chemotherapy response rate;and 6)differences in prognosis and survival among patients with different gene mutations.Statistical analysis was performed using SPSS 25.0 and Origin software.Results:(1)General clinical data:A total of 150 newly diagnosed patients with acute myeloid leukemia were included in this study,with a male-to-female ratio of approximately 1.31:1(86:64)and a median age of 56.50 years(15-83 years),including 85 patients under 60 years old and 65 patients aged 60 or older.According to the French-American-British(FAB)classification,4 cases were classified as M0(2.67%),17 cases as M1(11.33%),60 cases as M2(40%),24 cases as M4(16%),35 cases as M5(23.33%),and 10 cases were unclassified(6.67%).Patients with FLT3-ITD gene mutations had higher peripheral blood white blood cell counts,bone marrow blast percentages,and lactate dehydrogenase levels at initial diagnosis than those without the mutation,while patients with TET2 gene mutations had higher peripheral blood white blood cell counts and hemoglobin levels than patients with TET2 gene mutations tested negative during their initial diagnosis.Patients with NPM1 gene mutations tested positive had higher peripheral blood WBC counts and bone marrow primitive cell counts than those tested negative for NPM1 gene mutations,and the difference was statistically significant.(2)The NGS results of 150 patients showed that 132 patients had mutated genes,with a detection rate of 88%.Among the patients with gene mutations,at least one and up to 11 gene mutation sites were detected.Compared with patients under 60 years old,patients over 60 years old were more likely to have five or more multi-point mutations,and the difference was statistically significant..(3)The study results showed that the top 5 mutated genes with the highest mutation rates were:NPM1 mutation(33 cases,22.00%),FLT3-ITD mutation(33 cases,22.00%),TET2 mutation(31 cases,20.67%),DNMT3A mutation(27 cases,18.00%),and NRAS mutation(21 cases,14.00%).Among patients under 60 years old,the top 5 mutated genes were NPM1 mutation(17 cases,20.00%),FLT3-ITD(17 cases,20.00%),DNMT3A(13 cases,15.29%),NRAS(12 cases,14.12%),and TET2(11 cases,12.94%).Among patients aged 60 years and over,the top 5 mutated genes were TET2(20 cases,29.41%),NPM1(16 cases,24.62%),FLT3-ITD(16 cases,24.62%),DNMT3A(14 cases,21.54%),and ASXL1(13 cases,20.00%).Mutations of TET2,ASXL1,RUNX1,and SRSF2 were significantly increased in AML patients aged 60 years and over,with statistical significance,while GATA2 mutations were more frequent in patients under 60 years old,with statistical significance.(4)According to the grouping of chromosomal karyotypes,KIT mutations were most common in the low-risk group,accounting for 33.33%(4/12),NPM1 mutations were most frequent in the intermediate-risk group,accounting for 27.62%(29/105),and TP53 mutations were most frequent in the high-risk group,accounting for 37.04%(10/27).NPM1,DNMT3A,FLT3-ITD,and SRSF2 mutations were significantly increased in the intermediate-risk group,with statistical significance,while TP53 and PTPN11 were more common in the poor prognosis group,with statistical significance.The mutation rates of NPMl and CEBPA in normal karyotype were significantly higher than those in patients with abnormal karyotype,while the mutation rate of ASXL1 in abnormal karyotype was significantly increased,and the difference was statistically significant.(5)Studies have shown that there is coexistence and mutual exclusion between different mutated genes.For example,there is a significant coexistence between NPM1 mutation and FLT3-ITD mutation,NPM1 mutation and DNMT3A mutation,ASXL1 mutation and RUNX1 mutation.There were significant mutually exclusive relationships between FLT3-ITD mutation and TP53 mutation,TET2 mutation and IDH2 mutation,CEBPA mutation and NPM1 mutation.(6)The study showed that the CR rate and CRi rate of induction chemotherapy in the NPM1 wild group and the PTPN11 wild group was significantly higher than that in the mutant group,and the single gene mutation group had a lower induction response rate,and the ≤two gene mutation groups had a better induction response rate,and the difference was statistically significant.(7)Single-factor analysis display showed that age,efficacy after induction chemotherapy,FLT3-ITD mutation,DNMT3A mutation,PTPN11 mutation,single gene mutation,and ≤two gene mutations on OS were statistically significant.Age,efficacy after induction chemotherapy,NPM1 mutation,FLT3-ITD mutation,DNMT3A mutation,single gene mutation,≤2 gene mutations,≤3 gene mutations on RFS were statistically significant.The results of multivariate Cox regression analysis showed that age,efficacy after induction chemotherapy,FLT3-ITD,and DNMT3A mutations were independent factors affecting OS and RFS in adult AML patients.Conclusion:1.Clinical parameters of gene mutations are specific.FLT3-ITD gene mutation is often associated with high peripheral blood WBC count,high proportion of bone marrow blasts,and high LDH at initial diagnosis.TET2 gene mutation is associated with high peripheral blood WBC count and high Hb value at initial diagnosis,while NPM1 gene mutation is associated with high peripheral blood WBC count and high proportion of bone marrow blasts at initial diagnosis.2.≥ patients aged 60 years are more likely to have 5 or more multilocus mutations at the same time.3.The frequency of mutation of adult AML-related genes differs in different age groups.TET2,ASXL1,RUNX1,and SRSF2 mutations are more common in patients under 60 years of age,while GATA2 mutation has a significant increasing trend in patients under 60 years of age.4.There is coexistence or mutual exclusion of different gene mutations.Significant co-occurrence exists between NPM1 and FLT3-ITD,NPM1 and DNMT3A,and ASXL1 and RUNX1,while significant mutual exclusion exists between CEBPA and NPM1.5.The frequency of gene mutations in adult AML patients differs in different cytogenetic groups.KIT mutation is the most common in the low-risk cytogenetic group,while NPM1,DNMT3A,and FLT3-ITD mutations are common in the intermediate-risk cytogenetic group,and TP53 and PTPN11 mutations are more common in the poor prognosis group.NPM1 and CEBPA mutations are common in the normal cytogenetic group,while ASXL1 mutation rate is common in the abnormal cytogenetic group.6.The first-line chemotherapy response rate(CR rate+CRi rate)of the DNMT3A mutation group is significantly higher than that of the DNMT3A wild-type group,while the PTPN11 mutation group has a lower induction response rate than the PTPN11 wild-type group.7.Age,efficacy after induction chemotherapy,FLT3-ITD and DNMT3A mutations are independent risk factors for OS and RFS in adult AML patients. |
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